Antimicrobial peptides are ubiquitous in nature and play an important role in the innate immune system of many species. Many antimicrobial peptides are cationic, amphiphilic compounds that are believed to act by inducing pore formation in cell membranes. Antimicrobial peptides exhibit a broad spectrum of activity against microbes, and are believed to be immune to the development of resistance due to their non-specific mode of action. Peptides, however, are subject to proteolytic degradation and thus considerable effort has been devoted to synthesizing peptide mimetics, such as peptides comprised of D-isomers of amino acids, β-peptides and α-peptoids, which would be more stable to enzymatic hydrolysis.
β-Peptoids are N-substituted oligo-β-alanines (N-substituted β-aminopropionic acids) that were first described by Hamper, et al. (J. Org. Chem. (1998) 63:708-718). β-Peptoids are known to form random structures with high conformational freedom due to the absence of backbone hydrogen bonding. In addition, the tertiary amides of β-peptoids provide a backbone structure that is expected to be more stable to chemical or enzymatic hydrolysis than peptides.
Hamper, et al. (supra) described a method for the solid-phase synthesis of β-peptoids from a two-step, iterative reaction of resin-bound acrylate or acrylamides with primary amines followed by acryloylation of the resultant secondary amine with an acrylic acid derivative to regenerate the acrylamide. This method of synthesis was used to prepare β-peptoids comprising one to three N-substituted β-alanine residues. The antimicrobial activity of the β-peptoids synthesized by Hamper, et al., however, or of β-peptoids in general, is not known. The present invention provides novel β-peptoid polymers having antimicrobial activity.